Navigation Links
Researchers Develop Quick Way to Create Human Antibodies
Date:4/30/2008

Finding could speed development of vaccines for new flu strains, other health threats

WEDNESDAY, April 30 (HealthDay News) -- Researchers have devised a rapid and efficient method for generating protein sentinels of the immune system, called monoclonal antibodies, which mark and neutralize foreign invaders.

The development could potentially accelerate the traditionally challenging task of generating human antibodies, which can be used both to develop faster disease diagnostics -- for instance, to test for a new flu strain shortly after it emerges -- as well as safer and more effective medications, including vaccines.

"I think it's an important, incremental advance in our ability to provide antigen-specific monoclonal antibodies quickly and efficiently," said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases. He was not involved with the study, but the institute did fund some of the research.

The findings were published online April 30 in the journal Nature.

When a person is exposed to a germ or a vaccine, the immune system mounts a series of challenges to confront the foreign particles. One of those responses involves so-called B cells, which begin to secrete antibodies. Antibodies are proteins, and each binds to a specific three-dimensional shape, or antigen, on the pathogen's surface, blocking its ability to enter cells, or marking it for destruction by other immune cells.

Each B cell can make only one type of antibody. But because most antigens are relatively large, there may be several different B cells whose antibodies will bind to any given antigen. The resulting pool of antibodies is termed "polyclonal," because it arises from multiple clones of activated B cells.

A monoclonal antibody, as its name implies, is the product of a single B-cell clone, so it binds just to a single shape on the antigen's surface. Monoclonals are useful biotechnology tools and have proven effective in clinical settings, too: A handful of monoclonal-based therapeutics are commercially available, including the anti-cancer drug, Herceptin.

But few, if any, of these monoclonals are human proteins, said Patrick Wilson, of the Oklahoma Medical Research Foundation, who led the new study with Rafi Ahmed of Emory University School of Medicine. Instead, for both ethical and practical reasons, monoclonals are usually made in mice. And that's a problem, because the human immune system recognizes the mouse proteins as foreign and sometimes attacks them instead. The result can be an allergic reaction, and sometimes even death.

To get around that problem, researchers now "humanize" the antibodies, replacing some or all of mouse-derived pieces with human ones.

Wilson and Ahmed were interested in the immune response to vaccination. Conventional wisdom held that the B-cell response would be dominated by "memory" B cells. But as the study authors monitored individuals vaccinated against influenza, they found that a different population of B cells peaked about one week after vaccination, and then disappeared, before the memory cells kicked in. This population of cells, called antibody-secreting plasma cells (ASCs), is highly enriched for cells that target the vaccine, with vaccine-specific cells accounting for nearly 70 percent of all ASCs.

"That's the trick," said Wilson. "So instead of one cell in 1,000 binding to the vaccines, now it is seven in 10 cells."

All of a sudden, the researchers had access to a highly enriched pool of antibody-secreting cells, something that is relatively easy to produce in mice, but hard to come by for human B cells.

To ramp up the production and cloning of these antibodies, the researchers added a second twist. Mouse monoclonal antibodies are traditionally produced in the lab from hybridomas, which are cell lines made by fusing the antibody-producing cell with a cancer cell. But human cells don't respond well to this treatment. So Wilson and his colleagues isolated the ASC antibody genes and transferred them into an "immortalized" cell line. The result was the generation of more than 100 different monoclonals in less than a year, with each taking just a few weeks to produce.

That's a far cry from the one to two years typically required to make a single monoclonal cell line, Wilson noted.

Said Fauci: "The advance here is that now when you vaccinate someone, you can have literally within a week these very important antibody-secreting cells that can serve as the source for developing monoclonal antibodies. [ASCs] come earlier, they are in abundance, and have high-affinity antibodies. So that's a pretty important advance in cases where you need monoclonal antibodies for a pathogenic antigen."

In the event of an emerging flu pandemic, for instance, this approach could lead to faster production of human monoclonals to both diagnose and protect against the disease, he said.

More information

To learn more about therapeutic monoclonal antibodies, visit the American Cancer Society.



SOURCES: Patrick Wilson, Ph.D., assistant member, Oklahoma Medical Research Foundation, Oklahoma City; Anthony Fauci, M.D., director, U.S. National Institute of Allergy and Infectious Diseases; April 30, 2008, Nature, online


'/>"/>
Copyright©2008 ScoutNews,LLC.
All rights reserved

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... 13, 2017 , ... Lori R. Somekh, founder of the Law Office ... of elder law and special needs planning attorneys. “Membership in ElderCounsel helps our office ... forum to network with elder law attorneys nationwide,” said Somekh. , ElderCounsel ...
(Date:10/13/2017)... ... 2017 , ... The Visiting Nurse Association (VNA) of Somerset Hills is proud ... and unique items from across the nation, this holiday-themed event will raise funds and ... the VNA. The boutique will be open Saturday, November 4 (10:00 a.m. – ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The House ... most popular and least understood books in the Holy Scriptures, Revelation. The Book of ... baffled scholars for centuries. Many have tossed it off as mere rubbish, but Yisrayl ...
(Date:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of a ... “The Journey: From the Mountains to the Mission Field” is the creation of published ... all ages and currently teaches a class of ladies at her church, which she ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent ... sleep apnea using cutting-edge Oventus O2Vent technology. As many as 18 million ... by frequent cessation in breathing. Oral appliances can offer significant relief to about ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... , Oct. 10, 2017   West Pharmaceutical ... innovative solutions for injectable drug administration, today shared the ... ID Adapter for improving the intradermal administration of polio ... Skin Vaccination Summit in May 2017 by Dr. ... Polio Department, World Health Organization (WHO), and recently published ...
(Date:10/4/2017)... Oct. 4, 2017 OBP Medical ... illuminating medical devices, today announced regulatory approval from ... Agency (or Agência Nacional de Vigilância Sanitária (ANVISA)) ... cordless surgical retractor with integrated LED light source ... illumination and exposure of a tissue pocket or ...
(Date:10/2/2017)... 2017 The Rebound mobile app is poised to ... the tide of prescription drug addiction. The app empowers users ... and stepping down their dosage in a safe, controlled manner ... 2017; the first 100,000 people to sign up will enjoy ... ...
Breaking Medicine Technology: